Project 5: Dynamics of Aging and Extreme Longevity The broad long-term objectives of this project are to identify the dynamic mechanisms regulating relationships between indices of physiological and biological aging, health status and life span in humans and animals, and to use this knowledge in evaluation of the determinants of healthy life span and extreme longevity. In these analyses, we will investigate critical information about the regularities of the aging process accumulated in epidemiological, demographic, and experimental studies of aging and life span in different species. Four specific aims will be addressed: 1) Evaluate the role of age trajectories of physiological indices and other factors in the life span of long-lived individuals of both sexes using longitudinal data from the Framingham Heart Study and Honolulu Heart Study, determining how those age trajectories are associated with extreme longevity; 2) Evaluate the role of age trajectories of health-related indices and other factors in the life span of long-lived individuals of both sexes using data from National Long Term Care Survey, Longitudinal Study of Aging Danish Twins, Determinants of Healthy Longevity in China, Danish Study of 1905 birth cohort, Sardinia Longevity Study, identifying age trajectories of health related and other indices associated with extreme longevity; 3) Evaluate the role of genes and the environment in extreme longevity of the nematode worm C. elegans, investigating mechanisms of individual adaptation to changing environmental conditions in forming age patterns of mortality at extreme ages, and identifying combinations of genetic and environmental factors leading to extreme longevity; 4) Evaluate the hidden capacity of a fruit fly's organism to extend its longevity by changing regimes of nutrition and reproduction, identifying combinations of dietary conditions and age pattern of reproduction leading to extreme longevity. The work on all four aims will involve development of new mathematical and computer models and statistical methods for the analyses of data collected in human and animal studies of aging and longevity.